The investigations represent an attempt to understand the malformations of dentofacial development in the fetus caused by the administration of excess Vitamin A to the pregnant mother. Emphasis is placed on determining the alterations in cellular development and function which underlie and give rise to the gross morphological defects. An integrated study of dentofacial development in the A/Jax mouse fetus under normal, hypervitaminosis A and inhibited hypervitaminosic A conditions will be performed using histochemical and autoradiographic techniques for the analysis at the cellular level of those biological and biochemical systems in which vitamin A may participate. Histochemical techniques will be used mainly for analysis of alterations in lysosomal enzymes. The techniques of soluble- compound autoradiography as well as ordinary autoradiography are being used to study the distribution of isotopically labelled 3H-vitamin A in cellular areas of the developing mouth and face under normal and hypervitaminosis A conditions in order to determine if the quantity and/or distribution of the vitamin in the cells of the oral-facial region are directly related to morphological or metabolic alterations produced in these cells by hypervitaminosis A. For comparison purposes, parallel studies, using cortisone as a dentofacial teratogenic agent will also be performed to gain insight into the mechanisms of dentofacial development.